Z-oxazolidone compounds and proc



Patented Mar. 9, 1948 Z-GXAZOLIDONE COMPOUNDS AND PROC- ESS FOR PREPARING THE SAME August H. Homeyer, Webster Groves, Mo., as-

signor to Mallinckrodt Chemical Works, St. Louis, Mo., a corporation of Missouri No Drawing. Original application February 13,

1942, Serial No. 430,741.

Divided and this application February 16,1946, Serial No. 648,206

24 Claims. (01. 260-307) This invention rel-ates to five- -membered ring I compounds, and more particularly to z-oxazolidones.

This application is a division of my copending application Serial No. 430,741, filed February 13,

Among the objects of this inventionare the preparation of new compounds of the 2-oxazolidone series; the provision of a convenient method for making z-oxazolidones; and the provision of an improved method for the economical preparation of compounds of this type. Other objects will be in part obvious and in part pointed out hereinafter.

-The invention accordingly omprises the ingredients and combinations of ingredients, the proportions thereof, steps and sequence of steps, and features of composition and synthesis, analysis, or metathesis, which will be exemplified in the products and processes hereinafter described, and the scope of the application of which will be indicated in the following claims.

According to the present invention, z-oxazoliclones are prepared bythe reaction of a ,B-amino alcohol and an alkyl carbonate. The reaction may be represented by the following equation:

In the above equation, the Rs are selected from hydrogen, alkyl radicals, hydroxy alkyl radicals,

V 2 sary to cause the reaction to take place at ordinarily available conditions. Suitable catalysts are, for example, sodium methylate, magnesium methylate, potassium hydroxide and sodium carbonate, although other alkaline metallic compounds may be substituted. Although the function of the catalyst has not been completely determined, it is believed that the active element is in all cases a metal alkyl carbonate formed from the catalyst which is actually added.

p-Amino alcohols in general are suitable, even though they contain an additional functional group. These amino alcohols will react with one equivalent of alkyl carbonate to give the 2-oxazolidone. The resulting 2-oxazolidone may, however, be made to undergo further reaction with the alkyl carbonate where an additional functional group is present, to give more complex products.

The reaction materials must be free of. moisture before the reaction will begin. Thesystem stituted alkyls or aryls are likewise suitable, as

are aralkyls.

The following examples tion:

. EXAMPLE 1 v Ethanolamine A three-necked flask was fitted with a mechanical stirrer and an eflicient fractionating column. Ethanolamine (61 g.), diethyl carbon-ate (150 ml.), and sodium methylate (0.5 g.) were placed in the flask. The reaction mixture was stirred and the flask was heated in an oil bath. As the reaction progressed, alcohol was formed. and was removed as distillate at the head of the column. A total of 112 ml. of alcohol, correspondmg" to tWo moles per mole ofethanolamine, was obtained.v The residue in the flask solidified on cooling; itwas recrystallized from 100 ml. of chloroform. Two crops of 2-oxazolidone were obtained, weighing a total of 57 g., and representing ofthe theoretical yield. The product melted at 87-89" C. I I

2-oxazolidone (3 g.) was acetylated by'bolling with acetic anhydride (20 m1.) and. sodium aceillustrate the inven-- tate (1 g.) for 1.5 hours. Excess acetic anhydride was distilled off under reduced pressure and the residue was recrystallized from a mixture of benacne and ether. After sublimation in a high vac uum at 65 C. the pure 3-acetyl-2-oxazolidone melted at 69-70 C. It was soluble in water and its solution was neutral to litmus. Analysis of the new compound gave 10.9% nitrogen, compared to the theoretical calculated for C5H'703N of 10.85%.

Boiling 2-oxazolidone (9 g.) with acetyl chloride (11 ml.) for one hour was accompanied by the evolution of hydrogen chloride. Recrystallization of the residue from a mixture of benzene and ether gave the 3-acetyl derivative which was identical with the product obtained by the action of acetic anhydride.

ethyl carbonate (210 ml.) were placed in the apparatus described in Example 1. The system dioxide. The yield of 4-ethyl-2-oxazolidone was 57 g. It melted at 16-16.5 C. and its index of refraction was n 1.4631. The product was very soluble in water and the solution was neutral to litmus. Analysis of the new compound gave 52.1% carbon, 7.8% hydrogen and 12.3% nitrogen, compared to the theoretical calculated for C5H9O2N of 52.2%, 7.8% and 12.2% respectively.

bonate (350 ml.) were placed in the apparatus was dried by distilling off moist diethyl carbonate (40 ml.) The flask was cooled and sodium methylate (0.5 g.) was added as a catalyst, and then heating was continued. As the reaction progresses, alcohol was formed and a total of 115 ml. was obtained as distillate. Excess diethyl carbonate was removed by distillation under reduced pressure. The residue solidified on cooling. The product was purified by recrystallization from a mixture of alcohol and petroleum ether. The yield of 4,4-dimethyl-2-oxazolidone was 83 g. or 72% of the theoretical. The product melted at '55-56 0., and was very soluble in water, alcohol or benzene. Analysis of the new compound gave 522% carbon, 7.9% hydrogen, and 12.2% nitrogen, compared to the theoretical calculated for C3H902N of 52.2%, 7.8% and 12.2% respectively. Determination of the molecular weight gave 112, compared to the theoretical of 115.

EXAMPLE 3 Z-amz'no-Z -methyZ-1 propa'nol ml.) were collected as distillate in 35 minutes.

From the residue a good yield of 4,4-dimethyl-2- oxazolidone, identical with the product produced in Example 2, was obtained.

EXAMPLE 4 Z-amino-l-butanol Z-amino-l-butanol (89 g.) and diethyl .ca-rbonate (350 ml.) were placed in the apparatus described in Example 1, and the system was dried by distilling under 200 mm. pressure until 55 ml.

of diethyl carbonate had been collected. Sodium methylate (1 g.) was addedas a catalyst and the reaction mixture was heated at atmospheric pressure. Alcohol was formed. as the reaction proceeded, and a total of 120 mlpwas collected as distillate, Excess diethyl carbonate was distilled off under reduced pressure. The residue was crystallized from a mixture of chloroform and petroleum ether by cooling with solid carbon described in Example 1, and the system was dried by distilling until '50 ml. of diethyl carbonate had been-collected. Sodium methylate (1 g.) was added as a catalyst and heating was continued until .55 ml. of alcohol had been collected as distillate. The reaction mixture was filtered, ex-

cess diethyl carbonate was removed by distillation under reduced pressure, and the residual oil was fractionated through an indented column. 4-methyl-5-propyl-2-oxazolidone was an oil which boiled at 133 C. at 1.5 mm. pressure and its index of refraction was n 1.4581. The yield was 62 g. Analysis of the new compound gave 58.8% carbon, and 9.0% hydrogen, compared to the theoretical calculated for C7H13O2N of 58.7% and 9.1% respectively.

EXAMPLE 6 DiethanoZam-ine Diethanolamine g.), diethyl carbonate g.), and sodium methylate (0.5 g.) were placed in the apparatus described in Example 1, and heated at atmospheric pressure. Alcohol was formed as the reactionprogressed, a total of 115 ml. being collected in 1.25 hours; this corresponds to two moles of alcohol per mole of diethanolamine. Excess diethyl carbonate was removed by distillation under reduced pressure. The residue of crude 3(2-hydroxyethyl) -2-oxazo1idone was a viscous liquid which was soluble in water and insoluble in ether. A sample was purified by molecular distillation me. high vacuum at about 175 C. Analysis of the new compound gave 46.0% carbon, and 6.7% hydrogen, compared to the theoretical calculated for C5H903N of 45.8% and 6.9% respectively.

A sample of the product (3.5 g.) was dissolved in a little chloroform and phenylisocyanate (2.8 g.) dissolved in ether was added. The solvents were boiled off and the residue was recrystallized from benzene. The phenyl urethane 0f 3-(2-hydroxyethyl)-2-oxazolidone melted at 101-102 C. Analysis of the new compound gave 11.2% nitrogen, compared to the theoretical calculated for (312H14O2N2 of 11.2%

3-(2-hydroxyethyl) -2-oxazolidone (2.5 g.) and benzoyl chloride (2.5 ml.) were heated at 100 C. until hydrogen chloride was no longer evolved. The product was crystallized from methyl alcohol by cooling in solid carbon dioxide and then from a mixture of methyl alcohol and ether. It was sublimed in a high vacuum at C. The benzoate of 3-(2-hydroxyethyl)-2-oxazolidone melted at 69-70 C. Analysis of the new compound gave 5.95% nitrogen, compared to the theoretical calculated for C12H13O4N of 5.95%.

EXAMPLE 7 2-am2'n0 -1 -p'henyZ-1 -propanol 2-amino-l-phenyl-l propanol (50 g.) .and diethyl carbonate (.350 ml.) were placed in the apparatus described in Example 1, and the system was dried by distilling until 25 ml. diethyl carbonate had been collected. Sodium methylate (1 g.) was added and heating was continued until 38 ml. of alcohol had been obtained as distillate. The reaction mixture was filtered and excess diethyl carbonate was removed by distillation under reduced pressure. The residue was dissolved in chloroform and mixed with petroleum ether. The solid which separated weighed 21 g. After removing the solvent from the mother liquor, the residue was a viscous oil which weighed 37 g. The solid and the oil thus obtained repreto crystallize. The solid which separated was retallization from anhydrous alcohol (75 ml.) gave a first crop weighing 50 g., and a second crop weighing 14 g. The pure 4-methyl-4-hydroxymethyl-Z-oxazolidone melted at 115-1165 C. The product sublimed in a high vacuum at 135 C. It was soluble in water and the solution was neutral to litmus. Analysis of the new compound gave 46.0% carbon, 6.7% hydrogen, and 10.7% nitrogen, compared to the theoretical calculated for C5H9O3N of 45.8%, 6.9% and 10.7% respectively.

A sample of the product (4.4 g.) was mixed with phenyl isocyanate (6 ml.) and heated at 100 C. for 1.5 hours; The product solidified on cooling and was recrystallized from a mixture of chloroform and ether. The phenyl urethane of 4methyl-4hydroxymethyl2-oxyazolidone melted at 133-134 C. It was soluble in methyl alcohol, acetone or chloroform, and insoluble in water or ether. Analysis gave 11.3% nitrogen, compared to the theoretical calculated for C12H14O4N of 11.2%.

EXAMPLE 10 Monoethyl ethanolamine crystallized, and then sublimed in a high vac- Ephedrine Ephedrine alkaloid (16.5 g.) and dipropyl carbonate (40 g.) were placed in the apparatus described in Example 1, and the system was dried by distilling at a pressure of 100 mm. until 15 ml. of dipropyl carbonate had been collected. Sodium methylate (0.2 g.) was added and the reaction mixture was heated at atmospheric pressure in an oil bath at 160 C. The temperature of the reaction mixture was about 131 C., and 14 ml. of propyl alcohol, B. P. 95 C., were collected as distillate. Then the pressure was reduced to 100 mm. and excess dipropyl carbonate was distilled on". The residue was a liquid which solidified on cooling. It was recrystallized from benzene and washed with ether. The yield of 3.4-dimethyl5-phenyl-2-oxazolidone was 17 g. or 89% of the theoretical.

The product melted at 90-92 C., sublimed in a high vacuum at 90 C., was soluble in chloroform or benzene, and less soluble in water or ether. The solution in water was neutral to litmus. Analysis gave 7.3% nitrogen, compared to the theoretical calculated for C11H13O2N of 7.3% The compound was levo rotatory, [al being 95 when 0.6563 g. of the substance was made up to ml. of solution with 95% alcohol.

EXAMPLE 9 2amino-2-methyZ-1,3-propanediol 2-amino 2 methyl-1,3-propanediol (52.5 g.) and diethyl carbonate (59 g.) were placed in the apparatus described in Example 1 and heated by an oil bath. Alcohol began to be collected at the head of the column when the temperature of the reaction mixture was 120 C. A total of 44 g. of alcohol was collected as distillate in two hours. At the end of the heating period, the temperature solidified on cooling. It weighed 65 g. Recrys- Monoethyl ethanolamine (45 g.) and diethyl carbonate (350 ml.) were placed in the apparatus described in Example 1 and the system was dried by distilling at 200 mm. pressure until 50 ml. of diethyl carbonate had been collected. Sodium methylate- (1 g.) was added, and heating was continued at atmospheric pressure until 58 ml. of alcohol had been obtained as distillate. Fractionation gave two products; 3-ethyl-2-oxazolidone (42 g.), B. P. 92 C. at 1 mm., 12 1.4490; and anoil, B. P. C. at 1 mm., n 1.4308. The 3-ethyl-2-oxazolidone was soluble in water, giving a solution which was neutral to litmus; the pure compound appeared to be hydroscopic.

Analysis of the new compound gave 11.4% nitrogen, compared to the theoretical calculated for C5H902N of 12.1%.

The oil, B, P. 105 C. at 1 mm., was the ethyl carbonic ester of N-ethyl-N-(p-hydroxyethyl) urethane:

Analysis gave 6.0% nitrogen, compared to the theoretical calculated for C1oH1905N of 6.0%.

EXAMPLE 11 Monoethyl ethanolamine (15 ml.) was added, and the reaction mixture was heated to about C. at atmospheric pressure. Methanol (13 ml.) and butyl alcohol (40 ml.) were obtained as distillate in one hour. Fractionation of the product gave 3-ethyl-2-oxazoli- 'done, B, P, 78 C. at 0.5 mm., n 1.4490. The

product was identical with the 3-ethyl-2-oxazolidone obtained in Example 10.

EXAMPLE 12 Mono-n-butyl ethanolamine Mono-n-butyl ethanolamine (58.5 g.), dibutyl carbonate (102 g.) and toluene (40 ml.) were placed in the apparatus described in Example 1. The toluene was distilled off to dry the system. Potassium hydroxide (1 g.) was added as a catalyst, and heating was continued at 690 mm. pres- L chen-ass sure} 10 ml. "of butyl alcohol lo'eing obtained-as distillate in 0.5"hour. The rea'ctionm'ixture was filtered to-"remove the-little solid.matten'present.

Fractionation gave 3-n-butyl- 2 oxazolidone; B; P.

94 C. at 1 mm., n 1. 1515. The yield"was 83%.

Analysis l of the newbompound gave 9 .5 l nitrogen, compared to the theoretical calculatedior C7H1302N Oi 9.3%.

' EXAMPLE 13 Phenyl ethanolamine I Phenyl ethanol amine(68.5 g.), 'dibutyl'car- .bonate' (102 g.) and toluene (40 ml.) were placed i in the apparatus described in Example 1, and the toluene was distilled off to drythe system. Anhydrous sodium carbonate (1 g.) Wa's'added, and heating was continued at about" 170! Chat atmospheric pressure. Butyl alcohol was formed'rapidly,"90 ml. being collected as distillateliin 0.5

- dueiwas aiviscous oilWeighingJSO gfi This was mixed with 50 ml. anhydrous alcohol andTallowed to"c'rystallize,.yielding 46 g.'0f a solid product. The mother" liquor was stripped" of alcohol-, and the residuewas mixed with 100ml; methyl alco- 1101 and cooled in solid carbon dioxide. A'second crop of solid product weighing '28 g. was obtained,

making a total off-74 g. T The'remainderpfthe material failed to crystallize.

The solidproduct'was purified by recrystallization from alcohol. It melted at 106 102? C.,

' could not be sublimed,-and was soluble inwater,

. bonate having the .structure shown below,

. hourw-Aiter cooling, the reaction product was dissolved inho-t chloroform '(150 ml.),. treated with decolorizing carbon, and allowed to crystallize. .The product was washed with petroleum ether.- Atotal. of v81 g. of 3-phenyl-2-oxazoli done-M. 3.1204225? C., was obtairied.. Anal ysis. of the product gave 8.3% nitrogen, compared to the. theoretical calculated forCeHeOzNof 8.6

EXAMPLE 14 Tris- (hydro'xymethyl) "aminom'ethane Tris- (hydroxymethyl) -aminomet-hane (60.5 g.) dipropyl carbonate ('?6 g.) and .toluene 4100 ml.) were placed in the apparatus describedzin Example 1. The system was driedhydistilling until 15 ml. of toluene had been collected. 'After addition of sodium methylate (0.5 g) propyl alcohol was formed; and a mixture of it with toluene was taken oif as distillate. The residue remaining in the reaction flask was a syrupy liquid which was dissolved in'hot water';-'the'-solution was filtered and evaporated to dryness. :==Theresidue was purified by'crystallization from acetone and then from anhydrous alcohol. (hydroxymethyl) -2-oxazol idone melted at 109- 110 C.; it was soluble in-water; giving a solution which was neutral to. litmus.

. A sample of product "(.0.5..g.) .an-d. benzoyl chloride (1.5 ml.)-were heated.together-for.'1.5

hours. The solid residue was heatedwith-ldml. anhydrous v alcohol to destroy. excess benzoyl chloride, andpurified .by recrystallization from 95% alcohol. The benzoyl derivative melted at EXAMPLE 15 Diethanolamine Diethan olamine (105 g.) di'ethyl carbonate (300.1111), and sodiumxmethylate'lwfi. g.)*wwere placed in theiapparatus .describecl ini'EXample 1.

The 4,4-di- Analysisgave' 45.85% carbon;.5.38% ,hydrogen, and 9.96% nitrogen, compared to the theoretical calculated for C16I-I25O1oN3 of 45.82%, 6.01%, and 10.01% respectively; The molecular Weight found was ificompare'd to the theoretical of 419.

i EXAMPLE 16 2-amino-2-methyZ-1,3-propanediol Z-amino-2-methyl- 1;3=propane-diol (52.5 g.) and diethyl carbonate. (600 ml.) were placed in theapparatus described in Example 1. The reaction mixture .Was heated at atmosphericpressure byan oil bath at150. C. The. temperature of the liquid'in the flask was 130 C. and 45. ml. of diethylcarbonate, B. P.'123 C., were collected as distillate "during 30 minutes. Noalcohol was formed. After cooling somewhat, sodium methylate (1 g.) 'was'adcled as a catalyst. Then heating was resumed and alcohol was fractionated out of the reaction mixture at reduced pressure.

85 ml. of alcohol-were collected at48-50" C; under 200 mm. pressure during 'lfihours. This alcohol corresponded to 3 moles per mole of 2-amin'o-2- "'methyl-1,3-propanediol'used as starting material.

diethyl carbonate was removed by distillation under reduced pressure.r'Theresidue'was anoil which weighed 100 g. It was'solubleimwater, benzene acetic acid, or ethyl acetate; but'was insolubleinether] It failed to crystallize and attempts to distill it resulted in decomposition. Analysis of the new product gave 47.0%wcarbon, 6.5% hydrogen and 7.8% nitrogen.

Material similar to the product described above was produced also by the further-reaction of 4- methyl-e-hydroxymethyl-2 oxazolidone' with diethyl carbonate in" the: presence of a trace of sodium .methylate. 4e-methyllehydroxymethyl-Z- oxazolidonelZfi gJimm'EXampIe 9 and diethyl carbonate (300 ml;) were placed intheiapparatus "described- Example. 1. Theireactionzmixture was-heated at atmospheric pressureiand. 3.0 ml. of

diethyl carbonate-were collected: as distillate. No alcohol wasiormeda Sodiummethylate-(Ofi g.) was" dded as a catalyst, and. then 1'? mlqof. alcostillata-B. "394319 0., were collected. the temperature atthe head ofrthecolumn rose rapidly to the boiling point.- ofadiethylacan The amount of alcohol-correspondsto one mole per mole of the oxazolidone used as starting material. The reaction mixture was filtered to remove the trace of solid which had formed and excess diethyl carbonate was removed by distillation under reduced pressure. The residue was an oil which weighed 42 g. The material appeared to be entirely similar to the product described in the first paragraph of this example. Analysis of the product gave 46.8% carbon, 7.0% hydrogen and 7.8% nitrogen.

EXAMPLE 17 Trz's- (hydroxymethyl) aminomethanc Trls-(hydroxymethyl) -aminomethane (61 g.) and diethyl carbonate (650 ml.) were placed in the apparatus described in Example 1 and heated under 200 mm. pressure until 50 ml. of diethyl carbonate had been distilled off to dry the system. Sodium methylate (1 g.) was added as a catalyst and the mixture was heated at Mil-126 C. at atmospheric pressure while 120 ml. of alcohol were collected as distillate. The alcohol obtained corresponded to four moles per mole of the tris- (hydroxymethyl) -aminomethane. A yellowish, tally-like material separated from the diethyl carbonate and was removed by filtration; it weighed 69 g. After removal of excess diethyl carbonate from the mother liquor by distillation an oil remained as a residue. failed to crystallize and decomposed when sublimation was attempted. They were polymeric substances.

EXAMPLE 18 Z-amino-Z-methyl-I-propanol 2-amlno-Z-methyl-l-propanol (89 g.), di-sec.- butyl carbonate (191 g.), xylene (100 ml), and benzene (50 ml.) were combined in the apparatus described in Example 1 and 40 ml. of benzene were distilled off to dry the system. A suspension of potassium sec.-butyl carbonate (0.5 g.) in 25 ml. of-sec-butyl alcohol was added as a catalyst. The salt was prepared by dissolving potassium metal in sec.-butyl alcohol and saturating the solution with dry carbon dioxide. The reaction mixture was then heated at atmospheric pressure and 149 ml. of sec.-butyl alcohol was collected as distillate during two hours. The solvent, xylene, was removed by distillation under 110 mm. pressure. The residue remaining in the reaction flask was worked up for 4,4-dimethyl-2-oxazolidone as in Example 2. The yield was 74 g., or 65% of the theoretical.

EXAMPLE 19 all-Ephedrine d-Ephedrine (8.25 g.) and xylene (110 ml.) were placed in the apparatus described in Example 1. The system wasdried by distilling off ml. of xylene under 150 mm. pressure. Di-n-propyl carbonate (14.6 g.) was added, sodium methylate (9.2 g.) was added as a catalyst, and the reaction mixture was heated for two hours. Propyl alcohol (7 ml.) was collected as distillate. The solution remaining in the flask was treated with decolorizing carbon and then the solvent was removed by distillation under reduced pressure. The residue weighing 9.8 g. solidified on cooling. it was washed with petroleum ether and recrystallized from benzene and petroleum ether. The purified 3,4 edimethyl 5 phenyl- 2 -oxazolidone weighed 6.7 g. and melted at 92-925 C. The compound was dextro rotary [ul 5 being +94.5 when 6.5385 g. of the substance was made up to ml. of solution with 95% alcohol. 7

The products purities.

1o 1 EXAMPLE 20 dl-Norephedrine dl-Norephedrine (10 g.) diethyl carbonate (25 g.), xylene ml.) and benzene (25 ml.) were combined in the apparatus described in Example 1, and the system was dried by distilling until the benzene had been removed. After cooling somewhat, sodium methylate (0.3 g.) was added as a catalyst and heating was continued at atmospheric pressure for two hours. About 15 ml. of distillate were collected which contains about 5.7 ml. of alcohol. The reaction mixture was distilled to dryness under 50 mm. pressure. The residue crystallized on cooling. It was dissolved, in hot benzene and filtered to remove inorganic im- The filtrate was evaporated to a small volume and mixed with petroleum ether. The 4- methyl-5-phenyl-2-oxazolidone which. crystallized weighed 9.7 g. and melted at -146 C. A mixture of this product with the high melting diastereomeric isomer, described in Example 7, melted at 145-146 C.

EXAMPLE 21 Z-amz'no-I -phenyl-1 ;m'opanol 2-amino-l-phenyl-l-propanol (100 g.) and.

xylene (125 ml.) were combined in the apparatus described in Example 1, and the system was dried by distilling under mm, pressure until 30 ml. of xylene hadbeen collected. Diethyl carbonate (91.5 g.) and sodium methylate (0.5 g.) were added and heating was then continued at atmospheric pressure, 78 ml. of alcohol being collected during two hours. The hot solution remaining in the reaction flask was filtered and allowed to crystallize. The solid product which separated melted at SS-100 C. and weighed 86.5 g. The mother liquor was freed of solvent by distillation and there remained31.1 g. of a liquid residue. These products represent mixtures of the diastereomers of 4-methyl-5-pheny1-2-oxazolidone. By fractional crystallization of the solid product from benzene and absolute alcohol, there was obtained 4-methyl-5-phenyl-2-oxazolidone, M. P.

I LS-147 C., which was identical with that prepared from dl-norephedrine, as described in Example 20. mother liquors another diastereomer, M. P. 96-965 0., which is derived from dl-iso-norephedrine.

The z-oxazolidones are neutral substances soluble in water and organic solvents. They do not appear to form salts with acids or bases, nor do they appear to react with bromine. In general, their solubility in water decreases as thelength of the carbon chain substituents increases. They ar physiologically active. 7

Attention is directed to my copending applications, Serial Nos. 648,207 and 648,208, filed concurrently herewith.

In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.

As many changes could be made in the above methods'and products without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

I claim:

1. The method of making 2-oxazolidones which 7 There was also obtained from the 11 line metallic compound. catalyst under substantially anhydrousconditions, and condensing the moisture-free mixture to directly form a 2-oxa- ..zolidone.

T6 2. The method'ot-making- Z oxazolidones which aresubstituted in the 3.-posi tion -which:comprises mixing a monoethanolamine, the carbon: atom being; primary, a dialkyLcarbonateand analkaline". metallic compound catalyst. under. substan- 1 tiallys anhydrousconditions, and=heating:.the mix- ,.:ture: to directly condense the. monoethanolamine and carbonate to form a zeoxazolidone.

.t 3."The..method of making 2=oxazolidoneszwhich --are:substituted in the 3.- positionwhich comprises ;-'mi-xi-ng-:an N-substituted.monoethanolamine,.;.the

- wicarbonzatom being-primary; ardialkylcarhon- .-.a.te. and :an alkaline metallic-compound; catalyst -:under substantially..anhydrous aconditions. a d heating :themixture. to; directly, condense the .-monoethanolaminerand-q carbonate; to .form, a 1 2z-oxazol-idone.

4:7Themethod of making 2;-:oxazolidones which are substituted in the S-pOsitionj-which: comprises mixing an N-substitute'imonoethanolamine, the

a carbon atom being primary, with a dialkyl carbonate, said mixture inherently-containing mois- *.ture,; drying. said mixture;- adding an alkaline i emetallic compound catalyst, heating the resultant :zmixture punder. substantially. anhydrous condis'tions to di-rectlycondense themonoethanolamine -:.mix i -ng; an N-substituted monoethanolamine, the

- carbon atom --being .primary, with adialkyl-carb.onate, .said.mixtureinherentlycontaining moisture, ,heating .the mixture .under reduced pres- -':S'U.I&.'tO remove substantially allof said moisture, addinggan alkaline metallic compound catalyst to the moisture-free mixture, and heating.- the aresultant m xture. at. atmospheric pressure 'to edirectlyiorm. a 2-.oxazolidone.

. 'IJIhemethod of making 27QX3ZO1idOIl-ES which are substituted in. the 3 ,-.position which comprises :i mixing, an N-substitutedmonoethanolamine, the

- oecarbon atombeingprimary, Witha dialkyl carbonate, said mixture inherentlycontaining mois- .sture, heatingthemixture, todistilljofi aiminor proportion of the dialkyl ,carbonate. with "substantially all the moisture addinglas acatalyst an alkali. metal ,alcoholatee and-.condensing. the

x -eresultantmixtureito. directly form a 2-oxazolidone.

.8, The method.0.f... makine 2:.0XaZ0lidones which:

. .aresubstituted in, the 3-position which comprises ,mixi-ngan N -substituted. monoethanolamine, .the .1 .oc carbonatom being primary, with. a, .dialkyl carbonate, said mixture inherently oontainingmoisture, heating the mixture to distill. off ,moist dialkyl carbonate under reduced pressure condi- -.tions,...a.dding,,as a catalyst an alkaline earth "metal alcoholate, and .subiecting; the'mixture to .distillation. to directly condense ..the ,monolethanolamine-..and -carbonate. to form a 2e.oxazoli-.

lidone andmfor. continuously removing alcohol formed. in the a reaction.

. 9. The method .of making 3-ethyl-2-oxazolidone which comprises condensing monoethyle- .thanolamine with-diethyl carbonate to directly form B-ethyl-Z-oxazolidone.

. 10. The methodof making 3ethyl-2-oxazolidone which comprises preparing an anhydrous mixture of monethylethanolamine and a dialkyl carbonate, said reagents inherently containing moisture, addingto the resultant mixture an alkaline metal alcoholate as a catalyst, and heating theresultant' mixture to'directly form the 2,-oxazolidone and to distilloff alcohol formed by the. reaction.

511.. The ,method of, making 3-ethyl-2-oxazolidone which comprises mixing monoethylethanol- -amine with dibutyl carbonate, said mixture inherently containingmoisture, distilling themixture under reduced pressure until a minor proportionofthe dialkyl carbonate is removed with substantially all the. moisture contentv of the mixtureiadding. as a catalyst for the resultant .fmixture. magnesiuminethylate and heating the resultant mixture under atmospheric pressure to directly form the 2-oxazolidone and to.,distill.oif alcohol formed by the reaction.

$112...The .method'of making 3-n-butyl-2-oxazolidoneiwhich comprises preparing an anhydrous mixture. of,.mono-11-butylethanolamine. and a ..dialkyl carbonate, said reagents inherently .con-

taining moisture, adding to the resultant mixture an alkaline metallic compound as a catalyst, and heating the resultant mixture to directly form the 2-;oxazolidone :andto distilloff alcohol formed by the reaction.

1 131"The method of making 3-nbutyl-2-oxazolidone which comprises condensing. monon butylethanolamine with dibutyl carbonate to directly form 3-n-butyl-2-oxazolidone.

114. The methodof making 3-n-butyl-2oxazol "idone which comprises mixing mono-n-butylethanolamine with dibutyl carbonate and toluene, said mixture inherently containing moisture, distillingthe mixture .until the toluene is removed with substantially all the moisture content of the mixture,.adding as a catalyst for. the resultant ,mixture potassium hydroxide and heating the .resultantmixture under approximately atmospheric pressure to directly form the 2-oxazolidone and to distill ofi alcohol formed by the reaction,

15. The method of making 3-acetyl-2-oxazolidone which comprises preparing an anhydrous mixture of monoethanolamine and a dialkyl carbonate, adding to the resultant mixture an alkali metalalcoholate .as a catalyst, heating the resultantvmixture to directly form 2-oxazolidone and to distill oil alcohol formed by the reaction,

mixingmthe Z-oxazolidone with an acetylating agent and heating the mixture to form 3-acetyl- 16.; The method of making 3-acetyl-2-oxazolidone which comprises condensing monoethanolamine with diethyl carbonate to directly form 2-oxazolidone and acetylating the product.

l'lhThe method of making B-acetyl-Z-oxazolidone which comprises mixing anhydrous monoiethanolamine, diethyl carbonate and, sodium methylate, distilling the mixture to directly, form 2.-oxazolidone and to distill 0.1T alcohol formed by the reaction, mixing the product with acetic anhydride. andzsodium acetate and boiling the mixture, toform 3-acetyl-2-oxazolidone.

18. 3-acetyl-2-oxazolidone.

done which comprises condensing monoethanolamine with a dialkyl carbonate to directly form 2-oxazo1idone and acetylating the product.

AUGUST H. HOMEYER.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Name Date Homeyer Apr. 23, 1946 OTHER. REFERENCES Chemical Abstract, 1926, vol. 20, page 2682.

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